This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. My project focuses on the blood-milk barrier and its role in the milk excretion of xenobiotics (i.e., pharmaceuticals and environmental toxins). The long-term objective is to identify factors influencing the risk for adverse health effects in neonates and milk consumers as a result of exposure to harmful xenobiotics through milk. The objectives of this project are: 1) to characterize the blood-milk barrier with regard to transporter expression and their interaction with xenobiotics 2) identify factors affecting the expression and function of these transporters and 3) develop a valid in vitro model that can be used to study the kinetics and mechanisms of xenobiotic movement across the mammary epithelium. Two cell lines are being investigated for this latter purpose viz. BME-UV (bovine) and MCF10a (human). The laboratory techniques currently being used to address these objectives are cell culture, RT-PCR, Western Blot as well as flow-through and static diffusion cell systems. Envisioned outcomes include 1) a validated in vitro model that can be used to screen new and existing compounds to predict milk exposure for accurate toxicological risk assessments and 2) strategies targeting epithelial membrane transporters to minimize exposure to xenobiotics through milk.